|Publication number||US4778896 A|
|Application number||US 07/086,418|
|Publication date||Oct 18, 1988|
|Filing date||Aug 17, 1987|
|Priority date||Sep 4, 1986|
|Also published as||CA1302419C, DE3630046A1, EP0260485A1, EP0260485B1|
|Publication number||07086418, 086418, US 4778896 A, US 4778896A, US-A-4778896, US4778896 A, US4778896A|
|Original Assignee||Bayer Aktiengesellschaft|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (4), Non-Patent Citations (10), Referenced by (19), Classifications (9), Legal Events (5)|
|External Links: USPTO, USPTO Assignment, Espacenet|
The present invention relates to a new process for the preparation of 5-chloromethylpyridines, which can be used, for example, as intermediates for the preparation of insecticides.
It is already known that 5-chloromethylpyridines can be obtained by reacting 5-hydroxymethylpyridines with chlorinating agents, such as, for example, thionyl chloride (cf. EP-OS (European Published Specification) No. 163,855 and J. Het. Chem. 16, 333 (1979)). This process has the disadvantage that many reaction stages are necessary for the preparation of 5-chloromethylpyridines.
It is furthermore known that direct chlorination of the methyl group of 3-methylpyridines is not possible (cf. Helv. Chim. Acta 59, 179 ff (1976) and Angew. Chem. 1963, 236 ff).
It has now been found that 5-chloromethylpyridines of the general formula (I) ##STR3## in which R1 represents chlorine or nitro,
R2 represents chlorine, and
n represents the number 0 or 1,
are obtained when 5-methylpyridines of the formula (II) ##STR4## in which R1, R2 and n have the abovementioned meanings, are chlorinated at temperatures between 0° C. and 100° C., if appropriate in the presence of acid acceptors and if appropriate in the presence of inert diluents.
Surprisingly, the process according to the invention can successfully be used to prepare 5-chloromethylpyridines in a simple fashion and at low expense by direct chlorination of corresponding 5-methylpyridines. According to the state of the art, 4 complicated reaction stages are necessary for the preparation of 5-chloromethylpyridines: ##STR5## (cf. J. Org. Chem. 34, 3545 (1969) and J. Het. Chem. 16, 333 (1979)). This problematic reaction sequence can now be avoided in a surprisingly simple fashion.
The process according to the invention is preferred for preparing the following compounds of the formula (I): 2-chloro-, 2,3-dichloro-, 4-chloro , 2,4-dichloro- and 2-nitro-5-chloromethylpyridine.
The process according to the invention is particularly preferred for preparing the following compound of the formula (I): 2-chloro-5-chloromethylpyridine.
If 2-chloro-5-methyl-pyridine and elemental chlorine are used as starting materials in the process according to the invention, the reaction can be represented by the following equation: ##STR6##
Formula (II) provides a general definition of the 5-methylpyridines to be used as starting materials for the process according to the invention. In this formula, R1 and R2 preferably represent those radicals which are given above as being preferred or as being particularly preferred in the context of the definition of the substituents in the formula (I).
Examples of compounds of the formula (II) which may be mentioned are: 2-chloro-, 2,3-dichloro-, 4-chloro-, 2,4-dichloro- and 2-nitro-5-methylpyridine.
The compounds of the formula (II) are known or can be prepared in an analogous fashion by known processes.
The process, according to the invention, for the preparation of compounds of the formula (I) is preferably carried out using diluents. Suitable diluents in this process are virtually all inert organic solvents. These include, preferably, aliphatic, optionally halogenated hydrocarbons, such as methylene chloride, ethylene chloride, chloroform and carbon tetrachloride, ethers, such as diethyl and dibutyl ether, methyl tert.-butyl ether, glycol dimethyl ether and diglycol dimethyl ether, tetrahydrofuran and dioxane.
The process according to the invention is preferably carried out in the presence of acid acceptors. Acid acceptors which can be employed in the process according to the invention are all acid-binding agents which can conventionally be used for such reactions Preferably suitable are alkali metal carbonates, such as sodium carbonate and potassium carbonate, furthermore aliphatic, aromatic or heterocyclic amines, for example triethylamine, trimethylamine, dimethylaniline, dimethylbenzylamine, pyridine, 1,5-diazabicyclo-[4,3,0]-non-5-ene (DBN), 1,8-diazabicyclo-[5,4,0]-undec-7-ene (DBU) and 1,4-diazabicyclo-[2,2,2]-octane (DABCO).
The reaction temperatures can be varied within a relatively wide range in the process according to the invention. In general, the process is carried out at temperatures between 0° C. and 100° C. , preferably at temperatures between 40° C. and 80° C. . The process according to the invention is generally carried out under atmospheric pressure.
To carry out the process according to the invention in a preferred manner, elemental chlorine is passed through a mixture of starting material of the formula (II), acid acceptor and diluent, and the reaction mixture is stirred for several hours at the temperature necessary in each case (preferably in the range 40° to 80° C. ). Work-up is effected by generally conventional methods.
The 5-chloromethylpyridines to be prepared by the process according to the invention can be employed, for example, as intermediates for the preparation of nitromethylene derivatives which are effective as insecticides (cf. EP-A No. 163,855).
In this connection, the following further processing equation may be shown as an example: ##STR7##
Elemental chlorine is passed through a solution of 2.54 g (0.02 mol) of 2-chloro-5-methylpyridine and 4 g (0.0265 mol) of sodium carbonate in 10 ml of carbon tetrachloride at 60° C. . The course of the reaction is followed by gas chromatography. After 10 hours, the reaction mixture is cooled and concentrated.
2.1 g (65% of theory) of 2-chloro-5-chloromethylpyridine are obtained. The structure is confirmed by 1 H NMR spectra.
1 NMR (CDCl3): δ=8.4 (d, 1H, --CH--N═), 7.73 (dd,1H, ##STR9## 7.35 (d, 1H, ##STR10## 4.57 (s, 2H, --CH2) ppm.
It will be appreciated that the instant specification and claims are set forth by way of illustration and not limitation, and that various modifications and changes may be made without departing from the spirit and scope of the present invention.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US3123608 *||Nov 8, 1961||Mar 3, 1964||Process for chlorination of side chains|
|US3931200 *||Jan 22, 1974||Jan 6, 1976||The Dow Chemical Company||Substituted pyridinylalkoxy-, pyridinylalkylsulfonyl- and pyridinylalkylthio- phenylureas|
|US4205175 *||Feb 7, 1979||May 27, 1980||Imperial Chemical Industries Limited||Chlorination process|
|EP0163855A1 *||Apr 9, 1985||Dec 11, 1985||Nihon Tokushu Noyaku Seizo K.K.||Nitromethylene derivatives, intermediates, and process for their preparation as insecticides|
|1||*||F. E. Ziegler and J. G. Sweeny, J. Org. Chem., 34, 3545 3548, (1969).|
|2||F. E. Ziegler and J. G. Sweeny, J. Org. Chem., 34, 3545-3548, (1969).|
|3||*||H. Fritz, C. D. Weis and T. Winkler, Helv. Chim. Acta, 59, 170 190, (1976).|
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|7||*||Synthesis, Nr. 8, Aug. 1984, Seiten 676 679; G. R. Newkome et al: Alpha methyl functionalization of electron poor heterocycles: free radical chlorination .|
|8||Synthesis, Nr. 8, Aug. 1984, Seiten 676-679; G. R. Newkome et al: "Alpha-methyl functionalization of electron-poor heterocycles: free radical chlorination".|
|9||*||W. Mathes and H. Schuly, Angew. Chem., 235 240, (1963).|
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|Citing Patent||Filing date||Publication date||Applicant||Title|
|US5103011 *||Jan 23, 1991||Apr 7, 1992||Bayer Aktiengesellschaft||Preparation of 2-chloro-5- methyl-pyridine|
|US5198549 *||May 13, 1991||Mar 30, 1993||Bayer Aktiengesellschaft||Side-chain chlorination of alkylated nitrogen heteroaromatics|
|US5324841 *||Feb 24, 1993||Jun 28, 1994||Central Glass Company||Method of chlorinating side chain of 2-chloro-methylpyridine|
|US5508410 *||Nov 30, 1993||Apr 16, 1996||Reilly Industries, Inc.||Process for preparing 2-halo-5-substituted pyridines|
|US5521316 *||May 20, 1994||May 28, 1996||Cytec Technology Corp.||Chloroalkyl pyridinum hydrochloride compounds and processes for their preparation|
|US5623076 *||Dec 18, 1995||Apr 22, 1997||Bayer Aktiengesellschaft||Process for the preparation of chloromethylpyridines|
|US5686619 *||Mar 6, 1995||Nov 11, 1997||Cytec Technology Corp.||Chloroalkyl pyridinium hydrochloride compounds and processes for their preparation|
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|CN102796039A *||Aug 16, 2012||Nov 28, 2012||浙江工业大学||Method for continuous preparation of 2-chloro-5-chloromethylpyridine in microchannel|
|CN102796039B *||Aug 16, 2012||Nov 12, 2014||浙江工业大学||Method for continuous preparation of 2-chloro-5-chloromethylpyridine in microchannel|
|U.S. Classification||546/304, 546/345, 546/346|
|International Classification||C07D213/61, C07D213/26|
|Cooperative Classification||C07D213/26, C07D213/61|
|European Classification||C07D213/26, C07D213/61|
|Aug 17, 1987||AS||Assignment|
Owner name: BAYER AKTIENGESELLSCHAFT, LEVERKUSEN, GERMANY A CO
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNOR:GALLENKAMP, BERND;REEL/FRAME:004775/0942
Effective date: 19870807
Owner name: BAYER AKTIENGESELLSCHAFT,GERMANY
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:GALLENKAMP, BERND;REEL/FRAME:004775/0942
Effective date: 19870807
|Jun 20, 1989||CC||Certificate of correction|
|Nov 18, 1991||FPAY||Fee payment|
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|Mar 14, 1996||FPAY||Fee payment|
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|Mar 20, 2000||FPAY||Fee payment|
Year of fee payment: 12